Platinum Crosslinked Carbon Dot@TiO2−x p‐n Junctions for Relapse‐Free Sonodynamic Tumor Eradication via High‐Yield ROS and GSH Depletion

Abstract Sonodynamic therapy as a promising noninvasive modality is being developed for tumor therapy, but there is a lack of next‐generation sonosensitizers that can generate full ROS at high yields and simultaneously deplete elevated levels of glutathione (GSH) in tumor cells. Semiconductor p‐n junctions are engineered as high‐efficacy sonosensitizers for sonodynamic tumor eradication using pyridine N‐doped carbon dots (N‐CDs) as a p ‐type semiconductor and oxygen‐deficient TiO 2− x nanosheets as a n ‐type semiconductor. The rate constants of 1 O 2 and •OH generation by ultrasound‐excited N‐CD@TiO 2− x p‐n junctions are 4.3 and 4.5 times higher than those of TiO 2 , respectively. A Z‐scheme carrier migration mechanism in the p‐n junction achieving the rapid spatial separation of the ultrasound‐generated electron–hole pairs for enhanced full ROS production is proposed. GSH‐cleavable, Pt‐crosslinked, N‐doped CD fluorescent probes to detect the presence of intracellular GSH are also constructed. A GSH‐responsive, p‐n junction platform (Pt/N‐CD@TiO 2− x ) with integrated GSH detection, GSH depletion, and enhanced sonodynamic performance is then assembled. Malignant tumors are completely eradicated without relapse via intravenous administration of low‐dose Pt/N‐CD@TiO 2− x under ultrasound irradiation. This work substantiates the great potential of biocompatible, GSH‐responsive p‐n junctions as next‐generation sonosensitizers via p‐n junction‐enhanced ROS generation and metal ion oxidation of intracellular GSH.